Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma

• Published in: Oncogene Vol. 28; no. 26; pp. 2476 - 2484
• Main Authors: Lee, S -G, Jeon, H -Y, Su, Z -Z, Richards, J E, Vozhilla, N, Sarkar, D, Van Maerken, T, Fisher, P B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-07-2009; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Apoptosis; Astrocytes; Astrocytes - metabolism; Biological and medical sciences; Cancer; Cell activation; Cell Adhesion Molecules - deficiency; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Biology; Cell growth; Cell Line, Tumor; Cell physiology; Cell Proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; Children; Fetus - cytology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genes; Genetic aspects; Human Genetics; Humans; Internal Medicine; Kinases; Medical sciences; Medicine; Medicine & Public Health; Melanocytes; Melanocytes - metabolism; Metastases; Mice; Molecular and cellular biology; N-Myc Proto-Oncogene Protein; Neural crest; Neural stem cells; Neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neuroblastoma cells; Neurology; Nuclear Proteins - metabolism; Oncogene Proteins - metabolism; Oncology; original-article; Overexpression; Pathogenesis; Pathology; Peripheral nerves; Peripheral Nerves - cytology; Peripheral Nerves - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Physiological aspects; Progenitor cells; Proto-Oncogene Proteins c-akt - metabolism; Risk factors; Signal Transduction; siRNA; Solid tumors; Tumors of the nervous system. Phacomatoses; United States; neuroblastoma; AEG-1; MYCN; Akt; PI3K; Nervous system diseases; Pathogenesis; Neuroglia; Akt protein kinase; Malignant tumor; Astrocyte; Neuroblastoma; Carcinogenesis; Gene; Autonomic neuropathy; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2009.93

Neuroblastoma, derived from neural crest progenitor cells, is the most common extracranial solid tumor of childhood. Astrocyte elevated gene-1 (AEG-1) is a primary mediator of tumor progression and metastasis in several human cancers. In this study, we investigated the potential contribution of AEG-1 in human neuroblastoma pathogenesis. AEG-1 expression was significantly elevated in neuroblastoma patient-derived samples and neuroblastoma cell lines as compared with normal peripheral nerve tissues, normal astrocytes and immortalized melanocytes. Knockdown of AEG-1 by small interfering RNA reduced the tumorigenic properties of highly aggressive neuroblastoma cells. Conversely, over-expression of AEG-1 enhanced proliferation and expression of the transformed state in less aggressive neuroblastoma cells through activation of the phosphatidylinositol 3-kinase-Akt-signaling pathway and stabilization of MYCN. These provocative results indicate that AEG-1 may play a crucial role in the pathogenesis of neuroblastoma and could represent a potential target for therapeutic intervention.